Antibiotics (Abx) are the world's most prescribed class of drugs with a 25-30 billion $US global market. Numerous studies have shown that 40-70% of Abx are wrongly prescribed (Linder and Stafford 2001; Scott, Cohen et al. 2001; Davey, Brown et al. 2006; Cadieux, Tamblyn et al. 2007; Pulcini, Cua et al. 2007; 2011), making Abx the world's most misused drug (CDC 2011). Abx misuse can be classified into two types: (i) prescription to treat non-bacterial disease, such as a viral infection, for which Abx are ineffective and (ii) prescription in the case of a bacterial disease, but applying the wrong Abx spectrum. For example, according to the USA center for disease control and prevention over 60 Million wrong Abx prescriptions are given annually to treat flu in the US, for which they are ineffective and inappropriate. The major factors that limit the effectiveness of current diagnostic solutions for reducing erroneous prescription include: (i) time to diagnosis; (ii) inaccessible infection site; (iii) false positives due to non-pathogenic bacteria and (iv) the challenge of diagnosing mixed infection (i.e., bacterial and viral co-infection).
These factors are causing a diagnostic gap, which in turn often leads physicians to either over-prescribe Abx (the “just-in-case-approach”), or under-prescribe Abx (the “Wait-and-see-approach”) (Little and Williamson 1994; Little 2005; Spiro. Tay et al. 2006), both of which have far reaching health and financial consequences.
Ideally, a technological solution for assisting physicians in correctly prescribing Abx should enable diagnosis that: (i) accurately differentiates between a bacterial and viral infections; (ii) is rapid (within minutes); (iii) is able to differentiate between pathogenic and non-pathogenic bacteria that are part of the body's natural flora, (iv) can differentiate between mixed and pure viral infections and (v) is applicable in cases where the pathogen is inaccessible. Current solutions (such as culture, PCR and immunoassays) do not fulfill all these requirements: (i) most assays (with the exception of multiplex PCRs) are often constrained to a limited set of bacterial or viral strains; (ii) they usually require hours to days (e.g. culture and nucleic acid based assays); (iii) they often do not distinguish between pathogenic and non-pathogenic bacteria (Del Mar 1992); (iv) they are often incapable of distinguishing between a mixed and a pure viral infection and (v) they require direct sampling of the infection site in which traces of the disease causing agent are searched for. The latter prohibits diagnosis in cases where the pathogen resides in an inaccessible tissue, which is often the case.
Accordingly, a need exists for a method that accurately differentiates between bacterial viral and mixed infections.